解析SRAS病毒复制过程

　　

就在几年前，爆发了一场全球震惊的严重急性呼吸器官综合症（SARS）。引发SARS的病原是冠状病毒，一种正链RNA病毒，在宿主细胞的细胞浆里的胞内膜上复制，通过胞内膜获得复制需要的原料。在PloS Biology上，生物学家Eric Snijder和同事通过光学显微镜和切片电子显微镜中观察完整细胞里冠状病毒复制的过程。

 

病毒复制复合体是由大量的病毒蛋白和酶系统组成，对于这些蛋白和酶我们知之甚少。研究者通过显微镜观察病毒复制过程，从而了解病毒利用宿主细胞原料进行复制的过程，了解复制过程中病毒利用宿主原料的机制。

 

Snijder和同事使用电子显微镜技术和断层扫描技术对病毒复制过程的形态进行观察，并记录下这些形态结构。作者观察病毒与宿主间的相互作用，病毒利用宿主细胞原料的机制。这些研究结果可能为抗冠状病毒提供了新的药物靶位。

 

原文摘要：SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum

 

【Abstract】

Positive-strand RNA viruses, a largegroup including human pathogens such as SARS-coronavirus (SARS-CoV), replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morpho-genesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles DMVs)werepreviouslyimplicatedinSARS

CoVRNAsynthesis.Wehavenowappliedelectrontomographyofcryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200–300 nm), and ‘‘vesicle packets’’ apparently arising from MV merger.The convoluted membranes weremost abundantly immunolabeled forviral replicasesubunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virus-induced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this ‘‘replication network’’ will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions.

（生物通 张欢）